Pharmacological and biophysical characterization of voltage-gated calcium currents in the endopiriform nucleus of the guinea pig

Sara Brevi, Marco De Curtis, Jacopo Magistretti

Research output: Contribution to journalArticlepeer-review

Abstract

The endopiriform nucleus (EPN) is a well-defined structure that is located deeply in the piriform region at the border with the striatum and is characterized by dense intrinsic connections and prominent projections to piriform and limbic cortices. The EPN has been proposed to promote synchronization of large populations of neurons in the olfactory cortices via the activation of transient depolarizations possibly mediated by Ca2+ spikes. It is known that principal cells in the EPN express both a low- and high-voltage-activated (HVA) Ca2+ currents. We further characterized HVA conductances possibly related to Ca2+-spike generation in the EPN with a whole cell, patch-clamp study on neurons acutely dissociated from the EPN of the guinea pig. To study HVA currents in isolation, experiments were performed from a holding potential of -60 mV, using Ba2+ as the permeantion. Total Ba2+ currents (IBa) evoked by depolarizing square pulses peaked at 0/+ 10 mV and were completely abolished by 200 μM Cd2+. The pharmacology of HVA IBaS was analyzed by applying saturating concentrations of specific Ca2+-channel blockers. The L-type blocker nifedipine (10 μM; n = 11), the N-type-channel blocker ω-conotoxin GVIA (0.5 μM; n = 24), and the P/Q-type blocker ω-conotoxin MVIIC (1 μM; n = 16) abolished fractions of total IBaS equal on average to 24.7 ± 5.4%, 27,1 ± 3.4%, and 22.2 ± 2.4%, respectively (mean ± SE). The simultaneous application of the three blockers reduced IBa by 68.5 ± 6.6% (n = 10). Nifedipine-sensitive currents and most N- and P/Qtype currents were slowly decaying, the average fractional persistence after 300 ms of steady depolarization being 0.77 ± 0.02, 0.60 ± 0.06, and 0.68 ± 0.04, respectively. The residual, blocker-resistant (R-type) currents were consistently faster inactivating, with an average fractional persistence after 300 ms of 0,30 ± 0.08. Fast-decaying R-type currents also displayed a more negative threshold of activation (by about 10 mV) than non-R-type HVA currents. These results demonstrate that EPN neurons express multiple pharmacological components of the HVA Ca2+ currents and point to the existence of an R-type current with specific functional properties including fast inactivation kinetics and intermediate threshold of activation.

Original languageEnglish
Pages (from-to)2076-2087
Number of pages12
JournalJournal of Neurophysiology
Volume85
Issue number5
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

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